Rate of progression determines the clinical outcome after neural transplantation in Parkinson's disease

Abstract

Sir, I read with great interest the article by Piccini et al . (2005) analysing factors affecting the clinical outcome after foetal neural transplantation in Parkinson's disease. A recent review on the same topic emphasized the role of immunological mechanisms, tissue manipulation before grafting and graft placement (Winkler et al ., 2005), which can be of utmost relevance in explaining the negative final outcome shown by double-blind studies (Freed et al ., 2001; Olanow et al ., 2003). By using PET technology, Piccini et al . determined the amount of 18F-dopa uptake and 11C-raclopride binding in the grafted putamen, as well as in other areas that receive dopamine innervation, and correlated them with the clinical outcome during the first 2 years after transplantation. They found an increased 18F-dopa uptake in the grafted putamen in all patients. Patients with the worst outcome showed a parallel progressive reduction of 18F-dopa uptake in substantia nigra and median raphe region, as well as in the ventral striatum in which the uptake was reduced even before grafting. These areas are innervated by dopamine neurons located on the dorsal tier of the substantia nigra pars compacta and the ventral tegmental area. This suggests a continuing loss of dopaminergic neurons in substantia nigra despite a functioning graft that could affect the evolution of symptoms after transplantation. Thus, Piccini et al . state that the overall functional impact of dopamine neuron replacement is less pronounced in patients with more widespread …